Hb G Philadelphia heterozygotes may have 40 percent of Hb G in their blood, suggesting that an alpha-thalassemia gene may also be present. Among such subjects, however, some have unbalanced globin chain synthesis (alpha-thalassemic) but others have balanced (normal) synthesis. We believe that the latter have thalassemic and the former non-thalassemic deletions of the alpha chain genes. The alpha chain genes of these two classes of heterozygotes are being studied with restriction endonucleases in order to differentiate the nature of the two deletions. In addition, the structural abnormalities are being defined in a number of other inherited hemoglobin variants. Proteolytic enzymes in red cell precursors are being defined by their inhibition spectra. The relationship between carbonic anhydrase and fetal hemoglobin within the same cell are being studied by cytoimmunofluorescence techniques.